AB1431 EPIDEMIOLOGICAL AND GENETIC FEATURES OF ANTI-3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE NECROTIZING MYOPATHY IN NORTHERN SPAIN: SINGLE-CENTER EXPERIENCE
Authors: D. Prieto-Peña, J. G. Ocejo-Vinyals, J. A. Mazariegos-Cano, A. L. Pelayo, S. Remuzgo Martinez, F. Genre, A. García Dorta, M. Renuncio-Garcia, V. Martinez-Taboada, C. Garcia-Ibarbia, J. Sanchez-Martin, B. Atienza-Mateo, M. Lopez-Hoyos, R. Blanco, M. A. González-Gay, J. L. Hernández
Journal: Annals of the Rheumatic Diseases (2022)

Background Anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) is an entity of growing interest. However, data on epidemiology and clinical spectrum are still scarce and there is a need for the identification of its potential risk factors. Objectives To characterize the demographic, genetic, clinical, and serological features of patients with anti-HMGCR IMNM in a region of northern Spain. Methods Study of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference hospital in Northern Spain. Besides clinical and laboratory data, we analyzed the genetic influence of HLA genes and the rs4149056 (c.521T&gt;C) single nucleotide polymorphism (SNP) in the SLCO1B1 gene. Results 8 patients (5 women, 3 men) with a mean ± SD age of 64.9±7.3 years, fulfilled the criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years and the prevalence 3 per 100.000 population. All patients had dyslipidemia and had been exposed to statins. Seven of the 8 of cases complained of myalgia. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 of them. None of the patients had extra-muscular involvement. No evidence of malignancy was found. All patients had elevated serum CK levels with a median [IQR] of 4488 [2538-9194] IU/L. Serum 25-hydroxy vitamin D levels were decreased in all patients in whom it was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal levels of TSH at the time of diagnosis. All patients experienced improvement with different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population. Conclusion In northern Spain, the IMNM anti-HMGCR preferentially affects people over 50 years of age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a potential predisposing role in the development of this disease Table 1. Patient Age/Sex HLA DRB1*11 rs4149056 genotype MRC at the weakest muscle group* Dysphagia CK (IU/L) at diagnosis Anti-HMGCR titer (CU ) Induction therapy* Maintenance therapy Clinical improvement** CK (IU/L) at last follow-up visit 1 56/M Yes TT 2 No 8963 277.8 GC. IVIG.MTX GC. IVIG. MTX. RTX Marked 134 2 69/F Yes TT 0 Yes 9271 235.9 GC iv bolus. IVIG. GC. MTX. RTX. Marked 890 3 64/F Yes TT 3 No 4000 242.6 IVIG. IVIG.RTX Marked 1284 4 79/M Yes TT 4 No 4977 145.6 GC. IVIG. GC. IVIG. Complete 92 5 62/F No TT 3 No 2116 210.0 GC GC.MTX. Marked 236 6 57/F Yes TC 4 No 2294 259.3 IGIV IGIV Complete 235 7 68/F Yes TT 3 No 3273 236.0 GC. IGIV. AZA. GC. AZA Complete 249 8 64/M Yes TC 4 Yes 11000 179.0 GC iv bolus. AZA. GC. AZA Complete 161 AZA: azathioprine; CK: creatinine kinase; CU: chemiluminescence units; F: female; GC: glucocorticoids; IVIG: intravenous immunoglobulins; M: male; MRC: medical research council scale; MTX: methotrexate; RTX: rituximab; ** Induction therapy initiated within 3 months of diagnosis. **Clinical improvement: no improvement (no improvement in MRC grade), mild improvement (improvement of MRC grade but still requiring assistance for activities of daily living), marked improvement (persistence of mild weakness without functional limitation), and complete improvement (return to baseline with no symptoms or signs of weakness). Disclosure of Interests None declared